Sự chết theo chương trình - mạng lưới p53

Journal of Cell Science - Tập 116 Số 20 - Trang 4077-4085 - 2003
Abraham Rubinstein1, Michael Berger2, Zehavit Goldberg2, Ygal Haupt2
1Department of Pharmacy, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
2Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel

Tóm tắt

Việc tiếp xúc với căng thẳng tế bào có thể kích hoạt p53, một yếu tố phiên mã đặc hiệu theo trình tự, để thúc đẩy sự ngừng phát triển tế bào hoặc sự chết theo chương trình. Sự lựa chọn giữa những phản ứng tế bào này bị ảnh hưởng bởi nhiều yếu tố, bao gồm loại tế bào và căng thẳng, cũng như hoạt động của các hợp tác viên p53. p53 kích thích một mạng lưới tín hiệu rộng lớn hoạt động thông qua hai con đường chết theo chương trình chính. Con đường ngoại sinh, con đường thụ thể chết, kích hoạt sự phân giải pro-caspase thành caspase, trong khi đó con đường nội sinh, con đường ty thể, chuyển sự cân bằng trong gia đình Bcl-2 về phía các thành viên pro-apoptotic, thúc đẩy sự hình thành apoptosome, và do đó là sự chết theo chương trình do caspase điều hòa. Tác động của hai con đường chết theo chương trình này có thể được tăng cường khi chúng hội tụ thông qua Bid, mà là một mục tiêu của p53. Đa số các hiệu ứng chết theo chương trình này được trung chuyển thông qua việc kích thích các gen mục tiêu chết theo chương trình cụ thể. Tuy nhiên, p53 cũng có thể thúc đẩy sự chết theo chương trình bằng cơ chế độc lập phiên mã trong một số điều kiện nhất định. Do đó, một nhiều cơ chế khác nhau được p53 áp dụng để đảm bảo sự kích thích hiệu quả của sự chết theo chương trình theo cách đặc hiệu theo giai đoạn, mô và tín hiệu căng thẳng. Việc thao tác chức năng chết theo chương trình của p53 là một mục tiêu hấp dẫn cho liệu pháp điều trị ung thư.

Từ khóa


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